This proposal was designed to identify hereditary risk factors (genetic polymorphisms) that contribute to risk of youth suicide. Two methods are under study, each examining candidate genes in Utah's suicide victims. The methods include haplotype relative risk and direct mutation analysis. Previous research has indicated that factors contributing to suicide are both environmental and inherited. The serotonergic system has been implicated in impulsivity and suicidality, and tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin. The Principal Investigator has detected polymorphisms in intron 7 of the TPH gene, and this was studied in a sample of 66 suicide victims from the Utah Youth Suicide Study. Studies of polymorphisms at several loci in and surrounding this gene did not appear to be associated with suicide in this population. Additional loci are now being sought. DNA for these studies is obtained from post-mortem blood or other tissues made available through the Medical Examiner's office (located at the University Medical Center). Blood from pedigree members of probands who were suicide victims is collected under another IRB-approved study, entitled "A Community Approach for Investigating Suicide Among Teenagers and Young Adults in Utah" (IRB #5698-95).